Reproductive history and breast cancer prevention.

The hormonal milieu of an early full-term pregnancy induces lobular development, completing the cycle of differentiation of the breast. This process induces a specific genomic signature in the mammary gland that is represented by the stem cell containing a heterochomatin condensed nucleus (HTN). Even though differentiation significantly reduces cell proliferation in the mammary gland, the mammary epithelium remains capable of responding with proliferation to given stimuli, such as a new pregnancy. The stem cell HTN is able to metabolize the carcinogen and repair the induced DNA damage more efficiently than the stem cell containing an euchromatinic structure (EUN), as it has been demonstrated in the rodent experimental system. The basic biological concept is that pregnancy shifts the stem cell EUN to the stem cell HTN that is refractory to carcinogenesis. Data generated by the use of cDNA micro array techniques have allowed to demonstrate that while lobular development regressed after pregnancy and lactation, programmed cell death genes, DNA repair genes, chromatin remodeling, transcription factors and immune-surveillance gene transcripts all of these genes are upregulated and are part of the genomic signature of pregnancy that is associated with the preventive effect of this physiological process.